Maintenance of ANCA Vasculitis Remission by Intermittent Rituximab Dosing (MAINTANCAVAS)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
About this trial
This is an interventional treatment trial for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis focused on measuring rituximab, maintenance, remission
Eligibility Criteria
Inclusion Criteria:
- All patients must be able and willing to give written informed consent and comply with the requirements of the study protocol.
- Diagnosis: ANCA vasculitis as defined by a positive MPO- and/or PR3-ANCA test together with clinical features characteristic of ANCA-positive diseases as detailed in the 2012 Chapel Hill Consensus Conference Definitions(18).
- eGFR ≥ 30 cc/min/1.73m2
- Age: 18-82 years old
- Treated with rituximab-induced continuous B cell depletion and in remission (defined by a modified BVAS-WG=0 AND a prednisone dose of ≤ 7.5 mg) for at least 24 months.
- CD20 (B cells) undetectable at time of enrollment/randomization
- Urine Hcg negative for women of child bearing potential and not planning to become pregnant for at least 12 months from enrollment and at least 12 months after any study related rituximab dose
- Judged to be otherwise healthy by the Investigator, based on medical history and physical examination (no known active disease process for which life expectancy is less than 36 months)
Exclusion Criteria:
- Secondary Disease: disease suspected to be induced by levamisole-adulterated cocaine
- All transplanted patients
- Treatment: additional immunosuppressive agents other than rituximab and/or total daily prednisone dose ≥ 7.5 milligrams
- Hypogammaglobulinemia: IgG level < 250 mg/dL
- Terminal cancer or other primary illness with life expectancy of less than 36 months
- Active anti-GBM disease and other known autoimmune disease for which the need for additional immunosuppression is likely
- Pregnancy or breastfeeding
Sites / Locations
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
B cell reconstitution
Serologic ANCA flare
Subjects will not receive their regularly-scheduled every-six-month dose of rituximab and will instead receive rituximab 1000 mg IV x 1 dose once peripheral B cells return ( ≥ 10 B cells/mm3). This cycle will then re-start. Subjects will be seen in clinic every three months. Patients will continue to be dosed with rituximab each time the B cell count rises to 10 cells/mm3. In the unique scenario that the B cells are detectable, but less than the threshold of 10 cells/mm3, subjects will be asked to return in 6 weeks for repeat B cell testing.
Subjects will not receive regularly scheduled every six-month doses of rituximab (1000mg IV) and will instead be seen in clinic for ANCA titer monitoring every 3 months. Re-dosing will occur upon a significant ANCA titer increase. For MPO, a significant rise will be defined as a 5-fold rise in ANCA titer and a level greater than 4 times the cutoff value for the assay. For PR3, a significant rise will be defined as a 4-fold rise in ANCA titer to a level at least twofold above the cutoff for the assay. Subjects who sustain a significant increase in ANCA titer will receive rituximab 1000mg IV x 2 doses, spaced ~2-3 weeks apart. If the ANCA titer remains two-fold above baseline and above a specified threshold (the cutoff value of the assay for PR3 and 4 times the cutoff value for MPO) , subjects will continue to receive rituximab 1000mg IV every 6 months for a maximum of 2 doses, at which time a new baseline ANCA titer will be established and the cycle will re-start.